The Salivary Mycobiome Contains 2 Ecologically Distinct Mycotypes.

A broad range of fungi has been detected in molecular surveys of the oral mycobiome. However, knowledge is still lacking on interindividual variability of these communities and the ecologic and clinical significance of oral fungal commensals. In this cross-sectional study, we use internal transcribed spacer 1 amplicon sequencing to evaluate the salivary mycobiome in 59 subjects, 36 of whom were scheduled to receive cancer chemotherapy. Analysis of the broad population structure of fungal communities in the whole cohort identified 2 well-demarcated genus-level community types (mycotypes), with Candida and Malassezia as the main taxa driving cluster partitioning. The Candida mycotype had lower diversity than the Malassezia mycotype and was positively correlated with cancer and steroid use in these subjects, smoking, caries, utilizing a removable prosthesis, and plaque index. Mycotypes were also associated with metabolically distinct bacteria indicative of divergent oral environments, with aciduric species enriched in the Candida mycotype and inflammophilic bacteria increased in the Malassezia mycotype. Similar to their fungal counterparts, coexisting bacterial communities associated with the Candida mycotype showed lower diversity than those associated with the Malassezia mycotype, suggesting that common environmental pressures affected bacteria and fungi. Mycotypes were also seen in an independent cohort of 24 subjects, in which cultivation revealed Malassezia as viable oral mycobiome members, although the low-abundance Malassezia sympodialis was the only Malassezia species recovered. There was a high degree of concordance between the molecular detection and cultivability of Candida, while cultivation showed low sensitivity for detection of the Malassezia mycotype. Overall, our work provides insights into the oral mycobiome landscape, revealing 2 community classes with apparently distinct ecologic constraints and specific associations with coexisting bacteria and clinical parameters. The utility of mycotypes as biomarkers for oral diseases warrants further study.

Oral Mucosal Injury Caused by Targeted Cancer Therapies.

Targeted cancer therapies have fundamentally transformed the treatment of many types of cancers over the past decade, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. The unique mechanisms of action of these agents have resulted in many patients experiencing enhanced tumor response together with a reduced adverse event profile as well. Toxicities do continue to occur, however, and in selected cases can be clinically challenging to manage. Of particular importance in the context of this monograph is that the pathobiology for oral mucosal lesions caused by targeted cancer therapies has only been preliminarily investigated. There is distinct need for novel basic, translational, and clinical research strategies to enhance design of preventive and therapeutic approaches for patients at risk for development of these lesions. The research modeling can be conceptually enhanced by extrapolating "lessons learned" from selected oral mucosal conditions in patients without cancer as well. This approach may permit determination of the extent to which pathobiology and clinical management are either similar to or uniquely distinct from oral mucosal lesions caused by targeted cancer therapies. Modeling associated with oral mucosal disease in non-oncology patients is thus presented in this context as well. This article addresses this emerging paradigm, with emphasis on current mechanistic modeling and clinical treatment. This approach is in turn designed to foster delineation of new research strategies, with the goal of enhancing cancer patient treatment in the future.

Chemotherapy-induced oral mucositis and associated infections in a novel organotypic model.

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti-neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non-existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy-induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy-induced mucositis was developed based on a human oral epithelial cell line and a fibroblast-embedded collagen matrix. Treatment of organotypic constructs with 5-fluorouracil (5-FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three-dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5-FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E-cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5-FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5-FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy.

Oral mucosal injury in oncology patients: perspectives on maturation of a field.

In the past decade, there have been important strategic advances relative to pathobiological modeling as well as clinical management for oral mucositis caused by cancer therapies. Prior to the 1990s, research in this field was conducted by a relatively small number of basic and clinical investigators. Increasing interest among researchers and clinicians over the past twenty years has produced a synergistic outcome characterized by a number of key dynamics, including novel discovery models for pathobiology, increased experience in designing and conducting clinical trials, and creation of international collaborations among cancer care professionals who in turn have modeled clinical care paradigms based on state-of-the-science evidence. This maturation of the science and its clinical translation has positioned investigators and oncology providers to further accelerate both the foundational research and the clinical modeling for patient management in the years ahead. The stage is now set to further capitalize upon optimizing the interactions across this interface, with the goal of strategically enhancing management of patients with cancer at risk for this toxicity while reducing the cost of cancer care.

Report on World Workshops on Oral Medicine (WWOM) IV and V: research themes and citation impact: WWOM VI steering committee.

The first World Workshop on Oral Medicine (WWOM) was held in 1988. The portfolio has continued to expand in scope and impact over the past 26 years. Five World Workshops were conducted between 1988 and 2010, focusing on creation of systematic reviews in biomedicine and health care of importance to the international oral medicine community. WWOM VI was conducted in April 2014 and further extended this modeling. This most recent Workshop also fostered creation of the inaugural joint meeting between the American Academy of Oral Medicine and the European Association of Oral Medicine, together with The British Society for Oral Medicine and the Oral Medicine Academy of Australasia. The goal of the WWOM portfolio is to strategically enhance international oral medicine research, education, and clinical practice. To this end, this report summarizes subject areas for WWOM IV (2004) and research recommendations for WWOM V (2010), as well as citation metrics relative to publications from these two conferences. The information is designed to provide research and clinical context for key issues in oral medicine as delineated by the WWOM portfolio over the past 10 years, as well as for projected outcomes of WWOM VI over the next 12 months.

Using high throughput sequencing to explore the biodiversity in oral bacterial communities.

High throughput sequencing of 16S ribosomal RNA gene amplicons is a cost-effective method for characterization of oral bacterial communities. However, before undertaking large-scale studies, it is necessary to understand the technique-associated limitations and intrinsic variability of the oral ecosystem. In this work we evaluated bias in species representation using an in vitro-assembled mock community of oral bacteria. We then characterized the bacterial communities in saliva and buccal mucosa of five healthy subjects to investigate the power of high throughput sequencing in revealing their diversity and biogeography patterns. Mock community analysis showed primer and DNA isolation biases and an overestimation of diversity that was reduced after eliminating singleton operational taxonomic units (OTUs). Sequencing of salivary and mucosal communities found a total of 455 OTUs (0.3% dissimilarity) with only 78 of these present in all subjects. We demonstrate that this variability was partly the result of incomplete richness coverage even at great sequencing depths, and so comparing communities by their structure was more effective than comparisons based solely on membership. With respect to oral biogeography, we found inter-subject variability in community structure was lower than site differences between salivary and mucosal communities within subjects. These differences were evident at very low sequencing depths and were mostly caused by the abundance of Streptococcus mitis and Gemella haemolysans in mucosa. In summary, we present an experimental and data analysis framework that will facilitate design and interpretation of pyrosequencing-based studies. Despite challenges associated with this technique, we demonstrate its power for evaluation of oral diversity and biogeography patterns.

Genetics/epigenetics of oral premalignancy: current status and future research.

Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long-term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.

Strong and ductile colossal carbon tubes with walls of rectangular macropores.

We report a new type of carbon material-porous colossal carbon tubes. Compared with carbon nanotubes, colossal carbon tubes have a much bigger size, with a diameter of between 40 and 100 mum and a length in the range of centimeters. Significantly, the walls of the colossal tubes are composed of macroscopic rectangular columnar pores and exhibit an ultralow density comparable to that of carbon nanofoams. The porous walls of colossal tubes also show a highly ordered lamellar structure similar to that of graphite. Furthermore, colossal tubes possess excellent mechanical and electrical properties.

Major salivary gland damage in allogeneic hematopoietic progenitor cell transplantation assessed by scintigraphic methods.

Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell transplantation (HPCT). The investigation of major salivary gland dysfunction with sodium pertechnetate scintigraphy is a non-invasive method that provides images of the parotid and submandibular glands. In this prospective trial, 20 HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and 67Ga in order to evaluate the major salivary glands early involvement following HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30, +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc-pertechenate results did not demonstrate any functional differences between pre- versus post transplant periods. Results of the 67Ga scan revealed inflammatory infiltration following HPCT, primarily in submandibular glands, suggest a persistent involvement of major salivary glands up to Day +100 after HPCT.

The Window of Risk for Emigration of Wheat streak mosaic virus Varies with Host Eradication Method.

The wheat curl mite (WCM), Aceria tosichella, the vector of Wheat streak mosaic virus (WSMV), often survives the summer on volunteer wheat (Triticum aestivum) and may disperse from this "green bridge" in fall to newly planted winter wheat. Because some methods for managing volunteer wheat do not directly kill WCM, there is a window of risk for WCM and WSMV emigration after management has been applied. WCM survival in response to treatment of wheat by glyphosate, paraquat, stem cutting, and withholding water was measured in greenhouse experiments to determine how this window of risk for emigration varies with management. WCM populations on plants treated with paraquat or stem cutting decreased from the beginning of the sampling period. WCM populations on plants treated with glyphosate or that received no water increased up to 3 days after application and then decreased by 10 days after application. If glyphosate is used to manage volunteer wheat infested with WCM, it should be applied well before wheat is planted in fall. WCM in declining populations tended to be in an upright posture that could facilitate emigration via wind. The total green leaf area was strongly correlated with the number of WCM for treated plants and could be used in the field to predict the posttreatment survival of mites that pose a risk of emigration.

Ultralong single-wall carbon nanotubes.

Since the discovery of carbon nanotubes in 1991 by Iijima, there has been great interest in creating long, continuous nanotubes for applications where their properties coupled with extended lengths will enable new technology developments. For example, ultralong nanotubes can be spun into fibres that are more than an order of magnitude stronger than any current structural material, allowing revolutionary advances in lightweight, high-strength applications. Long metallic nanotubes will enable new types of micro-electromechanical systems such as micro-electric motors, and can also act as a nanoconducting cable for wiring micro-electronic devices. Here we report the synthesis of 4-cm-long individual single-wall carbon nanotubes (SWNTs) at a high growth rate of 11 microm s(-1) by catalytic chemical vapour deposition. Our results suggest the possibility of growing SWNTs continuously without any apparent length limitation.

Strongly enhanced current densities in superconducting coated conductors of YBa2Cu3O7-x + BaZrO3.

There are numerous potential applications for superconducting tapes based on YBa(2)Cu(3)O(7-x) (YBCO) films coated onto metallic substrates. A long-established goal of more than 15 years has been to understand the magnetic-flux pinning mechanisms that allow films to maintain high current densities out to high magnetic fields. In fact, films carry one to two orders of magnitude higher current densities than any other form of the material. For this reason, the idea of further improving pinning has received little attention. Now that commercialization of YBCO-tape conductors is much closer, an important goal for both better performance and lower fabrication costs is to achieve enhanced pinning in a practical way. In this work, we demonstrate a simple and industrially scaleable route that yields a 1.5-5-fold improvement in the in-magnetic-field current densities of conductors that are already of high quality.

Formation of pile networks by long carbon nanotubes from decomposition of CO on Co-Mo film.

We report the formation of pile networks by long carbon nanotubes grown at 700 degrees C from a Co-Mo film on a quartz plate. Carbon monoxide (CO) was used as the carbon source. The networks were formed because the density of catalyst particles on the substrate was low, which resulted in low carbon nanotube density that did not support vertical growth. At the same time, the low carbon nanotube density makes it possible for CO to reach the catalysts on the substrate for continuous growth. No obvious amorphous carbon chunks were observed, suggesting that the pile networks consisted of fairly high-quality, long carbon nanotubes.